Optical Tweezers: A Force to Be Reckoned With.

The 2018 Nobel Prize in Physics has been awarded jointly to Arthur Ashkin for the discovery and development of optical tweezers and their applications to biological systems and to Gérard Mourou and Donna Strickland for the invention of laser chirped pulse amplification. Here we focus on Arthur Ashkin and how his revolutionary work opened a window into the world of molecular mechanics and spurred the rise of single-molecule biophysics.

An Actin Network Dispatches Ciliary GPCRs into Extracellular Vesicles to Modulate Signaling.

Signaling receptors dynamically exit cilia upon activation of signaling pathways such as Hedgehog. Here, we find that when activated G protein-coupled receptors (GPCRs) fail to undergo BBSome-mediated retrieval from cilia back into the cell, these GPCRs concentrate into membranous buds at the tips of cilia before release into extracellular vesicles named ectosomes. Unexpectedly, actin and the actin regulators drebrin and myosin 6 mediate ectosome release from the tip of cilia. Mirroring signal-dependent retrieval, signal-dependent ectocytosis is a selective and effective process that removes activated signaling molecules from cilia. Congruently, ectocytosis compensates for BBSome defects as ectocytic removal of GPR161, a negative regulator of Hedgehog signaling, permits the appropriate transduction of Hedgehog signals in Bbs mutants. Finally, ciliary receptors that lack retrieval determinants such as the anorexigenic GPCR NPY2R undergo signal-dependent ectocytosis in wild-type cells. Our data show that signal-dependent ectocytosis regulates ciliary signaling in physiological and pathological contexts.

Thousands of conductance levels in memristors integrated on CMOS.

Neural networks based on memristive devices1-3 have the ability to improve throughput and energy efficiency for machine learning4,5 and artificial intelligence6, especially in edge applications7-21. Because training a neural network model from scratch is costly in terms of hardware resources, time and energy, it is impractical to do it individually on billions of memristive neural networks distributed at the edge. A practical approach would be to download the synaptic weights obtained from the cloud training and program them directly into memristors for the commercialization of edge applications. Some post-tuning in memristor conductance could be done afterwards or during applications to adapt to specific situations. Therefore, in neural network applications, memristors require high-precision programmability to guarantee uniform and accurate performance across a large number of memristive networks22-28. This requires many distinguishable conductance levels on each memristive device, not only laboratory-made devices but also devices fabricated in factories. Analog memristors with many conductance states also benefit other applications, such as neural network training, scientific computing and even 'mortal computing'25,29,30. Here we report 2,048 conductance levels achieved with memristors in fully integrated chips with 256 × 256 memristor arrays monolithically integrated on complementary metal-oxide-semiconductor (CMOS) circuits in a commercial foundry. We have identified the underlying physics that previously limited the number of conductance levels that could be achieved in memristors and developed electrical operation protocols to avoid such limitations. These results provide insights into the fundamental understanding of the microscopic picture of memristive switching as well as approaches to enable high-precision memristors for various applications. Fig. 1 HIGH-PRECISION MEMRISTOR FOR NEUROMORPHIC COMPUTING.: a, Proposed scheme of the large-scale application of memristive neural networks for edge computing. Neural network training is performed in the cloud. The obtained weights are downloaded and accurately programmed into a massive number of memristor arrays distributed at the edge, which imposes high-precision requirements on memristive devices. b, An eight-inch wafer with memristors fabricated by a commercial semiconductor manufacturer. c, High-resolution transmission electron microscopy image of the cross-section view of a memristor. Pt and Ta serve as the bottom electrode (BE) and top electrode (TE), respectively. Scale bars, 1 µm and 100 nm (inset). d, Magnification of the memristor material stack. Scale bar, 5 nm. e, As-programmed (blue) and after-denoising (red) currents of a memristor are read by a constant voltage (0.2 V). The denoising process eliminated the large-amplitude RTN observed in the as-programmed state (see Methods). f, Magnification of three nearest-neighbour states after denoising. The current of each state was read by a constant voltage (0.2 V). No large-amplitude RTN was observed, and all of the states can be clearly distinguished. g, An individual memristor on the chip was tuned into 2,048 resistance levels by high-resolution off-chip driving circuitry, and each resistance level was read by a d.c. voltage sweeping from 0 to 0.2 V. The target resistance was set from 50 µS to 4,144 µS with a 2-µS interval between neighbouring levels. All readings at 0.2 V are less than 1 µS from the target conductance. Bottom inset, magnification of the resistance levels. Top inset, experimental results of an entire 256 × 256 array programmed by its 6-bit on-chip circuitry into 64 32 × 32 blocks, and each block is programmed into one of the 64 conductance levels. Each of the 256 × 256 memristors has been previously switched over one million cycles, demonstrating the high endurance and robustness of the devices.

Structures and mechanisms of the Arabidopsis auxin transporter PIN3.

The PIN-FORMED (PIN) protein family of auxin transporters mediates polar auxin transport and has crucial roles in plant growth and development1,2. Here we present cryo-electron microscopy structures of PIN3 from Arabidopsis thaliana in the apo state and in complex with its substrate indole-3-acetic acid and the inhibitor N-1-naphthylphthalamic acid (NPA). A. thaliana PIN3 exists as a homodimer, and its transmembrane helices 1, 2 and 7 in the scaffold domain are involved in dimerization. The dimeric PIN3 forms a large, joint extracellular-facing cavity at the dimer interface while each subunit adopts an inward-facing conformation. The structural and functional analyses, along with computational studies, reveal the structural basis for the recognition of indole-3-acetic acid and NPA and elucidate the molecular mechanism of NPA inhibition on PIN-mediated auxin transport. The PIN3 structures support an elevator-like model for the transport of auxin, whereby the transport domains undergo up-down rigid-body motions and the dimerized scaffold domains remain static.

Retrotransposon-mediated evolutionary rewiring of a pathogen response orchestrates a resistance phenotype in an insect host.

Ongoing host-pathogen interactions can trigger a coevolutionary arms race, while genetic diversity within the host can facilitate its adaptation to pathogens. Here, we used the diamondback moth (Plutella xylostella) and its pathogen Bacillus thuringiensis (Bt) as a model for exploring an adaptive evolutionary mechanism. We found that insect host adaptation to the primary Bt virulence factors was tightly associated with a short interspersed nuclear element (SINE - named SE2) insertion into the promoter of the transcriptionally activated MAP4K4 gene. This retrotransposon insertion coopts and potentiates the effect of the transcription factor forkhead box O (FOXO) in inducing a hormone-modulated Mitogen-activated protein kinase (MAPK) signaling cascade, leading to an enhancement of a host defense mechanism against the pathogen. This work demonstrates that reconstructing a cis-trans interaction can escalate a host response mechanism into a more stringent resistance phenotype to resist pathogen infection, providing a new insight into the coevolutionary mechanism of host organisms and their microbial pathogens.

A Bayesian approach to estimate MHC-peptide binding threshold.

Major histocompatibility complex (MHC)-peptide binding is a critical step in enabling a peptide to serve as an antigen for T-cell recognition. Accurate prediction of this binding can facilitate various applications in immunotherapy. While many existing methods offer good predictive power for the binding affinity of a peptide to a specific MHC, few models attempt to infer the binding threshold that distinguishes binding sequences. These models often rely on experience-based ad hoc criteria, such as 500 or 1000nM. However, different MHCs may have different binding thresholds. As such, there is a need for an automatic, data-driven method to determine an accurate binding threshold. In this study, we proposed a Bayesian model that jointly infers core locations (binding sites), the binding affinity and the binding threshold. Our model provided the posterior distribution of the binding threshold, enabling accurate determination of an appropriate threshold for each MHC. To evaluate the performance of our method under different scenarios, we conducted simulation studies with varying dominant levels of motif distributions and proportions of random sequences. These simulation studies showed desirable estimation accuracy and robustness of our model. Additionally, when applied to real data, our results outperformed commonly used thresholds.

Structural mechanisms for the activation of human cardiac KCNQ1 channel by electro-mechanical coupling enhancers.

The cardiac KCNQ1 potassium channel carries the important IKs current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 structures have been recently resolved, the structural basis for the dynamic electro-mechanical coupling, also known as the voltage sensor domain-pore domain (VSD-PD) coupling, remains largely unknown. In this study, utilizing two VSD-PD coupling enhancers, namely, the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) and a small-molecule ML277, we determined 2.5-3.5 Å resolution cryo-electron microscopy structures of full-length human KCNQ1-calmodulin (CaM) complex in the apo closed, ML277-bound open, and ML277-PIP2-bound open states. ML277 binds at the "elbow" pocket above the S4-S5 linker and directly induces an upward movement of the S4-S5 linker and the opening of the activation gate without affecting the C-terminal domain (CTD) of KCNQ1. PIP2 binds at the cleft between the VSD and the PD and brings a large structural rearrangement of the CTD together with the CaM to activate the PD. These findings not only elucidate the structural basis for the dynamic VSD-PD coupling process during KCNQ1 gating but also pave the way to develop new therapeutics for anti-arrhythmia.

Optical torque calculations and measurements for DNA torsional studies.

The angular optical trap (AOT) is a powerful instrument for measuring the torsional and rotational properties of a biological molecule. Thus far, AOT studies of DNA torsional mechanics have been carried out using a high numerical aperture oil-immersion objective, which permits strong trapping but inevitably introduces spherical aberrations due to the glass-aqueous interface. However, the impact of these aberrations on torque measurements is not fully understood experimentally, partly due to a lack of theoretical guidance. Here, we present a numerical platform based on the finite element method to calculate forces and torques on a trapped quartz cylinder. We have also developed a new experimental method to accurately determine the shift in the trapping position due to the spherical aberrations by using a DNA molecule as a distance ruler. We found that the calculated and measured focal shift ratios are in good agreement. We further determined how the angular trap stiffness depends on the trap height and the cylinder displacement from the trap center and found full agreement between predictions and measurements. As a further verification of the methodology, we showed that DNA torsional properties, which are intrinsic to DNA, could be determined robustly under different trap heights and cylinder displacements. Thus, this work has laid both a theoretical and experimental framework that can be readily extended to investigate the trapping forces and torques exerted on particles with arbitrary shapes and optical properties.

Origin, evolution, and diversification of inositol 1,4,5-trisphosphate 3-kinases in plants and animals.

BACKGROUND: In Eukaryotes, inositol polyphosphates (InsPs) represent a large family of secondary messengers and play crucial roes in various cellular processes. InsPs are synthesized through a series of pohophorylation reactions catalyzed by various InsP kinases in a sequential manner. Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP3K), one member of InsP kinase, plays important regulation roles in InsPs metabolism by specifically phosphorylating inositol 1,4,5-trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP4) in animal cells. IP3Ks were widespread in fungi, plants and animals. However, its evolutionary history and patterns have not been examined systematically. RESULTS: A total of 104 and 31 IP3K orthologues were identified across 57 plant genomes and 13 animal genomes, respectively. Phylogenetic analyses indicate that IP3K originated in the common ancestor before the divergence of fungi, plants and animals. In most plants and animals, IP3K maintained low-copy numbers suggesting functional conservation during plant and animal evolution. In Brassicaceae and vertebrate, IP3K underwent one and two duplication events, respectively, resulting in multiple gene copies. Whole-genome duplication (WGD) was the main mechanism for IP3K duplications, and the IP3K duplicates have experienced functional divergence. Finally, a hypothetical evolutionary model for the IP3K proteins is proposed based on phylogenetic theory. CONCLUSION: Our study reveals the evolutionary history of IP3K proteins and guides the future functions of animal, plant, and fungal IP3K proteins.

Duloxetine protected indomethacin-induced gastric mucosal injury by increasing serotonin-dependent RANTES expression and activating PI3K-AKT-VEGF pathway.

Antidepressant duloxetine has been shown protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines are the principal mediators of inflammation. Thus, by screening the differential expression of cytokines in the gastric mucosa using cytokine array at 3 h after indomethacin exposure, when the gastric ulcer began to format, we found that indomethacin increased cytokines which promoted inflammation responses, whereas duloxetine decreased pro-inflammatory cytokines increased by indomethacin and increased RANTES expression. RANTES was consistently increased by pretreated with both 5 mg/kg and 20 mg/kg duloxetine at 3 h and 6 h after indomethacin exposure in male rats. Selective blockade of RANTES-CCR5 axis by a functional antagonist Met-RANTES or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin (5-HT), norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased 5-HT levels in platelet-poor plasma, while treatment with 5-HT promoted expression of RANTES in the gastric mucosa and alleviated the indomethacin-induced gastric injury. Furthermore, duloxetine activated PI3K-AKT-VEGF signaling pathway, which was regulated by RANTES-CCR5, and selective inhibitor of VEGF receptor axitinib blocked the prophylactic effect of duloxetine. Furthermore, duloxetine also protected gastric mucosa from indomethacin in female rats, and RANTES was increased by duloxetine after 6 h after indomethacin exposure too. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in gastroprotective effect of duloxetine against indomethacin, which advanced our understanding in inflammatory modulation by monoamine-based antidepressants.

Composite of carbon dots and TiNiSn thermoelectric materials: Initial investigation on the electrical and thermal transport properties.

TiNiCu0.025Sn0.99Sb0.01 is prepared using microwaves. However, an ultra-high electrical conductivity and electronic thermal conductivity are obtained by interstitial Cu and Sb doping, which could not effectively improve the ZT value. We introduce carbon dots (CDs) as a nano-second phase by ball milling to simultaneously optimize the thermoelectric properties. To our best knowledge, this is the first report on half-Heusler/CDs composites. Experimental results show that the introduction of nano-CDs optimizes the carrier concentration and mobility and dramatically improves the Seebeck coefficient through the energy filtering effect. The nano-CDs introduce more point defects, inhibit the grains growth, and form a specific carbon solid solution second phase in the matrix. The lattice thermal conductivity is reduced to the same level as TiNiSn at 1.96 W m-1 K-1 through the synergistic effect of point defects and phase and grain boundaries scattering, and the ZT value reaches a maximum of 0.63 at 873 K.

Voltage-gating and cytosolic Ca2+ activation mechanisms of Arabidopsis two-pore channel AtTPC1.

Arabidopsis thaliana two-pore channel AtTPC1 is a voltage-gated, Ca2+-modulated, nonselective cation channel that is localized in the vacuolar membrane and responsible for generating slow vacuolar (SV) current. Under depolarizing membrane potential, cytosolic Ca2+ activates AtTPC1 by binding at the EF-hand domain, whereas luminal Ca2+ inhibits the channel by stabilizing the voltage-sensing domain II (VSDII) in the resting state. Here, we present 2.8 to 3.3 Å cryoelectron microscopy (cryo-EM) structures of AtTPC1 in two conformations, one in closed conformation with unbound EF-hand domain and resting VSDII and the other in a partially open conformation with Ca2+-bound EF-hand domain and activated VSDII. Structural comparison between the two different conformations allows us to elucidate the structural mechanisms of voltage gating, cytosolic Ca2+ activation, and their coupling in AtTPC1. This study also provides structural insight into the general voltage-gating mechanism among voltage-gated ion channels.

Wireless and Battery-Free Sensor for Interstitial Fluid Pressure Monitoring.

Congestive heart failure (CHF) is a fatal disease with progressive severity and no cure; the heart's inability to adequately pump blood leads to fluid accumulation and frequent hospital readmissions after initial treatments. Therefore, it is imperative to continuously monitor CHF patients during its early stages to slow its progression and enable timely medical interventions for optimal treatment. An increase in interstitial fluid pressure (IFP) is indicative of acute CHF exacerbation, making IFP a viable biomarker for predicting upcoming CHF if continuously monitored. In this paper, we present an inductor-capacitor (LC) sensor for subcutaneous wireless and continuous IFP monitoring. The sensor is composed of inexpensive planar copper coils defined by a simple craft cutter, which serves as both the inductor and capacitor. Because of its sensing mechanism, the sensor does not require batteries and can wirelessly transmit pressure information. The sensor has a low-profile form factor for subcutaneous implantation and can communicate with a readout device through 4 layers of skin (12.7 mm thick in total). With a soft silicone rubber as the dielectric material between the copper coils, the sensor demonstrates an average sensitivity as high as -8.03 MHz/mmHg during in vitro simulations.

Kinematic and Joint Compliance Modeling Method to Improve Position Accuracy of a Robotic Vision System.

In the field of robotic automation, achieving high position accuracy in robotic vision systems (RVSs) is a pivotal challenge that directly impacts the efficiency and effectiveness of industrial applications. This study introduces a comprehensive modeling approach that integrates kinematic and joint compliance factors to significantly enhance the position accuracy of a system. In the first place, we develop a unified kinematic model that effectively reduces the complexity and error accumulation associated with the calibration of robotic systems. At the heart of our approach is the formulation of a joint compliance model that meticulously accounts for the intricacies of the joint connector, the external load, and the self-weight of robotic links. By employing a novel 3D rotary laser sensor for precise error measurement and model calibration, our method offers a streamlined and efficient solution for the accurate integration of vision systems into robotic operations. The efficacy of our proposed models is validated through experiments conducted on a FANUC LR Mate 200iD robot, showcasing notable improvements in the position accuracy of robotic vision system. Our findings contribute a framework for the calibration and error compensation of RVS, holding significant potential for advancements in automated tasks requiring high precision.

New insights into evolution and functional diversification of Camellia sinensis LRR-RLKs.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent the largest subgroup of receptor-like kinases (RLKs) in plants. While some LRR-RLK members play a role in regulating various plant growth processes related to morphogenesis, disease resistance, and stress response, the functions of most LRR-RLK genes remain unclear. In this study, we identified 397 LRR-RLK genes from the genome of Camellia sinensis and categorized them into 16 subfamilies. Approximately 62% of CsLRR-RLK genes are situated in regions resulting from segmental duplications, suggesting that the expansion of CsLRR-RLK genes is due to segmental duplications. Analysis of gene expression patterns revealed differential expression of CsLRR-RLK genes across different tissues and in response to stress. Furthermore, we demonstrated that CssEMS1 localizes to the cell membrane and can complement Arabidopsis ems1 mutant. This study is the initial in-depth evolutionary examination of LRR-RLKs in tea and provides a basis for future investigations into their functionality. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01458-1.

Regulating Perovskite Crystallization through Interfacial Engineering Using a Zwitterionic Additive Potassium Sulfamate for Efficient Pure-Blue Light-Emitting Diodes.

Quasi-two-dimensional (quasi-2D) perovskites are emerging as efficient emitters in blue perovskite light-emitting diodes (PeLEDs), while the imbalanced crystallization of the halide-mixed system limits further improvements in device performance. The rapid crystallization caused by Cl doping produces massive defects at the interface, leading to aggravated non-radiative recombination. Meanwhile, unmanageable perovskite crystallization is prone to facilitate the formation of nonuniform low-dimensional phases, which results in energy loss during the exciton transfer process. Here, we propose a multifunctional interface engineering for nucleation and phase regulation by incorporating the zwitterionic additive potassium sulfamate into the hole transport layer. By using potassium ions (K+ ) as heterogeneous nucleation seeds, finely controlled growth of interfacial K+ -guided grains is achieved. The sulfamate ions can simultaneously regulate the phase distribution and passivate defects through coordination interactions with undercoordinated lead atoms. Consequently, such synergistic effect constructs quasi-2D blue perovskite films with smooth energy landscape and reduced trap states, leading to pure-blue PeLEDs with a maximum external quantum efficiency (EQE) of 17.32 %, spectrally stable emission at 478 nm and the prolonged operational lifetime. This work provides a unique guide to comprehensively regulate the halide-mixed blue perovskite crystallization by manipulating the characteristics of grain-growth substrate.

Comparative transcriptome and metabolome analyses identified the mode of sucrose degradation as a metabolic marker for early vegetative propagation in bulbs of Lycoris.

Vegetative propagation (VP) is an important practice for production in many horticultural plants. Sugar supply constitutes the basis of VP in bulb flowers, but the underlying molecular basis remains elusive. By performing a combined sequencing technologies coupled with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry approach for metabolic analyses, we compared two Lycoris species with contrasting regeneration rates: high-regeneration Lycoris sprengeri and low-regeneration Lycoris aurea. A comprehensive multi-omics analyses identified both expected processes involving carbohydrate metabolism and transcription factor networks, as well as the metabolic characteristics for each developmental stage. A higher abundance of the differentially expressed genes including those encoding ethylene responsive factors was detected at bulblet initiation stage compared to the late stage of bulblet development. High hexose-to-sucrose ratio correlated to bulblet formation across all the species examined, indicating its role in the VP process in Lycoris bulb. Importantly, a clear difference between cell wall invertase (CWIN)-catalyzed sucrose unloading in high-regeneration species and the sucrose synthase-catalyzed pathway in low-regeneration species was observed at the bulblet initiation stage, which was supported by findings from carboxyfluorescein tracing and quantitative real-time PCR analyses. Collectively, the findings indicate a sugar-mediated model of the regulation of VP in which high CWIN expression or activity may promote bulblet initiation via enhancing apoplasmic unloading of sucrose or sugar signals, whereas the subsequent high ratio of hexose-to-sucrose likely supports cell division characterized in the next phase of bulblet formation.

Understanding the Origin and Evolution of Tea (Camellia sinensis [L.]): Genomic Advances in Tea.

Tea, which is processed by the tender shoots or leaves of tea plant (Camellia sinensis), is one of the most popular nonalcoholic beverages in the world and has numerous health benefits for humans. Along with new progress in biotechnologies, the refined chromosome-scale reference tea genomes have been achieved, which facilitates great promise for the understanding of fundamental genomic architecture and evolution of the tea plants. Here, we summarize recent achievements in genome sequencing in tea plants and review the new progress in origin and evolution of tea plants by population sequencing analysis. Understanding the genomic characterization of tea plants is import to improve tea quality and accelerate breeding in tea plants.

Origin, evolution and diversification of plant mechanosensitive channel of small conductance-like (MSL) proteins.

Mechanosensitive (MS) ion channels provide efficient molecular mechanism for transducing mechanical forces into intracellular ion fluxes in all kingdoms of life. The mechanosensitive channel of small conductance (MscS) was one of the best-studied MS channels and its homologs (MSL, MscS-like) were widely distributed in cell-walled organisms. However, the origin, evolution and expansion of MSL proteins in plants are still not clear. Here, we identified more than 2100 MSL proteins from 176 plants and conducted a broad-scale phylogenetic analysis. The phylogenetic tree showed that plant MSL proteins were divided into three groups (I, II and III) prior to the emergence of chlorophytae algae, consistent with their specific subcellular localization. MSL proteins were distributed unevenly into each of plant species, and four parallel expansion was identified in angiosperms. In Brassicaceae, most MSL duplicates were derived by whole-genome duplication (WGD)/segmental duplications. Finally, a hypothetical evolutionary model of MSL proteins in plants was proposed based on phylogeny. Our studies illustrate the evolutionary history of the MSL proteins and provide a guide for future functional diversity analyses of these proteins in plants.

Ultra-High Interfacial Thermal Conductance via Double hBN Encapsulation for Efficient Thermal Management of 2D Electronics.

Heat dissipation is a major limitation of high-performance electronics. This is especially important in emerging nanoelectronic devices consisting of ultra-thin layers, heterostructures, and interfaces, where enhancement in thermal transport is highly desired. Here, ultra-high interfacial thermal conductance in encapsulated van der Waals (vdW) heterostructures with single-layer transition metal dichalcogenides MX2 (MoS2 , WSe2 , WS2 ) sandwiched between two hexagonal boron nitride (hBN) layers is reported. Through Raman spectroscopic measurements of suspended and substrate-supported hBN/MX2 /hBN heterostructures with varying laser power and temperature, the out-of-plane interfacial thermal conductance in the vertical stack is calibrated. The measured interfacial thermal conductance between MX2 and hBN reaches 74 ± 25 MW m-2 K-1 , which is at least ten times higher than the interfacial thermal conductance of MX2 in non-encapsulation structures. Molecular dynamics (MD) calculations verify and explain the experimental results, suggesting a full encapsulation by hBN layers is accounting for the high interfacial conductance. This ultra-high interfacial thermal conductance is attributed to the double heat transfer pathways and the clean and tight vdW interface between two crystalline 2D materials. The findings in this study reveal new thermal transport mechanisms in hBN/MX2 /hBN structures and shed light on building novel hBN-encapsulated nanoelectronic devices with enhanced thermal management.